The aim of this study was to determine the effects of dietary supplementation with EFAs on disease activity and on key aspects of systemic and local immune function in patients with ulcerative colitis. After 6 months supplementation of the above, there was an improvement in the disease activity scores. In the essential fatty acids supplemented group (15 patients) compared with the placebo (15 patients) [median and range] (p<0.05). This was also associated with an improvement in the colonoscopic evaluation score in the EFAs group compared with the placebo [median and range] (p< 0.05). Analysis between the two groups showed significant reduction (p < 0.05) in the circulating numbers of CD2+, CD3+, CD4+, CD8+ CD16+ and CD56+. Cytokines analysis in the serum revealed reduction in the concentration of IL-2, IL-6, IL-8, IL-12, TNF-a and INF-g in the EFAs group. However, only IL-8 and Myeloperoxidase reduction was of statistical significance. On the other than there was elevation of IL-1ra and IL-10 in the EFAs group but only IL-10 elevation was statistically significant. Cytokines analysis in the washout showed corresponding reduction in IL-2, IL-6, IL-8 and elevation of in IL-1ra, IL-10 in the EFAs group. There was no significant change in IL-12, IL-15, TNF-a, INF-g, LTB4 and Myeloperoxidase. This study has demonstrated that omega-3 essential fatty acids appear to have a significant role in inducing and maintaining remission in patients with extensive ulcerative colitis. This clinical improvement was associated with changes in key aspects of systemic and local immune function in patients with ulcerative colitis.